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Effectiveness of Lofexidine to Prevent Stress-Related Opiate Relapse During Naltrexone Treatment - 1

This study has been completed.
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00142909
First received: September 1, 2005
Last updated: August 3, 2011
Last verified: August 2011
History of Changes
  Purpose

Lofexidine is an experimental medication that may be beneficial in reducing opiate withdrawal symptoms, such as sleep difficulty, anxiety, and tension. The purpose of this study is to determine whether lofexidine in combination with naltrexone can improve an individual's ability to cope with stress and subsequently increase the chances of remaining abstinent from opiates.


Condition Intervention Phase
Opioid-Related Disorders
 Drug: Lofexidine
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Lofexidine: Enhancing Naltrexone Treatment for Opiate Addiction

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:
  • Opioid withdrawal symptoms, opioid craving, rates of opioid relapse, and naltrexone treatment adherence measured at week 12; [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • blood pressure, adverse events; perceived stress ratings [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 120
Study Start Date: February 2005
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Lofexidine: Study medication
 Drug: Lofexidine
Participants will receive either A) lofexidine or B) placebo pill. The dosing will be initiation at 0.4 mg bid and increased to 0.8mg in week 1 and 1.0 and 1.2 mg bid in week 2, and maintained at 1.2mg bid for weeks 3 to 12. They are then tapered down to 0 over the course of four days in week 12. While the target dose will be 2.4 mg daily, if any subject shows reduced tolerability at this or a lower dose, the dose will be adjusted to the maximum tolerated dose for that subject.
Placebo Comparator: B
Placebo pill
 Drug: Lofexidine
Participants will receive either A) lofexidine or B) placebo pill. The dosing will be initiation at 0.4 mg bid and increased to 0.8mg in week 1 and 1.0 and 1.2 mg bid in week 2, and maintained at 1.2mg bid for weeks 3 to 12. They are then tapered down to 0 over the course of four days in week 12. While the target dose will be 2.4 mg daily, if any subject shows reduced tolerability at this or a lower dose, the dose will be adjusted to the maximum tolerated dose for that subject.

Detailed Description:

Naltrexone is a medication currently used to treat opiate dependence. Naltrexone blocks the euphoric effects of opiates. However, naltrexone treatment suffers from high rates of drop-out and relapse. One possible explanation for this is that opiate addicts continue to experience stress in early recovery from opiate dependence. Lofexidine is an experimental medication currently used in the United Kingdom for opiate detoxification and to treat opiate withdrawal symptoms, including sleep difficulty, muscle pain, anxiety, and tension. The purpose of this study is to examine whether lofexidine in combination with naltrexone can improve an individual's ability to cope with stress. The study will examine whether this, in turn, increases the likelihood that an individual remains abstinent from opiates and maintains recovery for a longer time period.

Participants in this 12-week, double-blind, placebo-controlled trial will be randomly assigned to receive either lofexidine or placebo while currently receiving standard naltrexone outpatient treatment. Lofexidine will be initiated at twice daily doses of 0.4 mg and increased to 0.8 mg by the end of Week 1. The doses will be increased to 1.2 mg by the end of Week 2, and maintained at this level for Weeks 3 through 12. During Week 12, lofexidine discontinuation will be tapered over 4 days. Hour-long study visits will occur 3 times each week to assess vital signs, medication side effects, and withdrawal symptoms. Blood, alcohol, and urine tests will be performed as well as a psychiatric evaluation. Administration of naltrexone will also occur 3 times each week. Follow-up visits will occur at Months 1 and 3 after discontinuation of lofexidine.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meets DSM-IV criteria for opioid dependence
  • Eligible to take a daily dose of 50 mg of naltrexone
  • Normal EKG
  • Able to read English

Exclusion Criteria:

  • Currently psychotic or psychiatrically disabled (e.g., suicidal, homicidal, manic)
  • Regular use of anticonvulsants, sedatives/hypnotics, prescription analgesics, antihypertensives (including clonidine), antiarrhythmics, antiretroviral medications, or tricyclic antidepressants
  • Underlying medical conditions, such as cerebral, kidney, thyroid, or cardiac pathology, and currently taking medications for any of these conditions
  • Abstinent from opiates for more than 4 weeks prior to initiation of naltrexone
  • Medical problems precluding naltrexone treatment, such as hepato-cellular injury, as evidenced by abnormal liver enzyme tests (greater than three times the normal level) and a history of cirrhosis
  • Hypotensive (resting blood pressure below 90/50 mm Hg)
  • Pregnant or breastfeeding
  • Use of an investigational drug within the 3 months prior to enrollment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00142909

Locations
United States, Connecticut
Yale University, Psychiatry
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Rajita Sinha Yale University
  More Information

No publications provided

Responsible Party: Rajita Sinha, Ph.D./ Professor, Yale University School of Medicine
ClinicalTrials.gov Identifier: NCT00142909     History of Changes
Other Study ID Numbers: NIDA-18219-1, R01-18219-1, DPMC
Study First Received: September 1, 2005
Last Updated: August 3, 2011
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Additional relevant MeSH terms:
Opioid-Related Disorders
Substance-Related Disorders
Mental Disorders
Naltrexone
Lofexidine
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
 Central Nervous System Agents
Therapeutic Uses
Antihypertensive Agents
Cardiovascular Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013